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1.
Clin Genet ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674016

RESUMO

Dent disease is a rare X-linked recessive inherited tubular disease. In this multicenter study, the clinical presentation and genetic background of Chinese children with Dent disease are studied to improve the cognition and diagnostic ability of pediatricians. In this prospective cohort, we described the genotype and phenotype of a national cohort composed of 45 pediatric probands with Dent disease belonging to 45 families from 12 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system. The CLCN5 gene from 32 affected families revealed 28 different mutations. The OCRL gene from 13 affected families revealed 13 different mutations. The incidence of low-molecular-weight proteinuria (LMWP) in both Dent disease type 1 populations and Dent disease type 2 populations was 100.0%; however, the incidence of other manifestations was not high, which was similar to previously reported data. Therefore, LMWP is a key clinical feature that should alert clinicians to the possibility of Dent disease. A high amount of LMWP combined with positive gene test results can be used as the diagnostic criteria for this disease. The diagnostic criteria are helpful in reducing the missed diagnosis of this disease and are beneficial for protecting the renal function of these patients through early diagnosis and early intervention. This article is protected by copyright. All rights reserved.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31669280

RESUMO

NK-lysins, a type of broad-spectrum antimicrobial peptide (AMP), act as an essential effector of innate defense against microbial attack in higher vertebrates and so in fish. The present study delineates the structural and functional characterization of NK-lysin from yellow catfish (Pelteobagrus fulvidrac) (Pelteobagrus fulvidraco). PfNK-lysin encodes a 153-residue peptide, which displays the hallmark features of other known NK-lysins with the ordered array of six well-conserved cysteine residues and five-exon/four-intron structure. It was found to be ubiquitous in tissues, being detected most abundantly in gill and head kidney. In vivo exposure to stimuli (LPS, PolyI:C, and Edwardsiella ictaluri) induced PfNK-lysin expression in head kidney and spleen. Synthetic PfNK-lysin-derived peptide exhibited in vitro bactericidal potency against both Gram-positive and Gram-negative bacteria, with the highest inhibitory effect on pathogen Edwardsiella ictaluri. Fluorescence microscopy and scanning electron microscopy further confirmed its capacity to cause damage to the bacterial plasma membrane. Taken together, these data suggest that PfNK-lysin might participate in antimicrobial defense of yellow catfish by membrane-disruptive action.

3.
J Clin Lab Anal ; : e23075, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659795

RESUMO

OBJECTIVE: To determine the clinical and liver stiffness characteristics of a cohort of Chinese patients with Hepatocellular carcinoma in different stages of Barcelona clinic liver cancer. METHODS: Details of 1180 patients with Hepatocellular carcinoma referred from October 2014 to November 2017 were collected retrospectively. Demographic data, etiology, clinical, and biochemical details were retrospectively analyzed. The changes of liver stiffness in different etiologies and different stages of Barcelona clinic liver cancer were especially analyzed. RESULTS: The onset age was 60.33 ± 9.11 (range 24-84) years, 9 cases were ≤40 years, 572 cases were 41-60 years, males accounted for 83.92%, females accounted for 16.08%; 599 cases were ≥61 years, males accounted for 78.25%, females accounted for 21.75%. Compared with males, the proportion of females ≥61 is higher than that of men. Majority (n = 787; 66.69%) had HBV infection; second commonest cause was HCV infection (n = 217; 18.39%). More patients with HBV infection were 41-60 years (69.06%) and were younger than HCV patients. There was no statistical difference in etiology, age, gender, and distribution of diabetes mellitus among different Barcelona clinic liver cancer stages (P > .05). The overall Hepatocellular carcinoma (HCC) was found to be positively correlated with alkaline phosphatase, γ-glutamyltransferase, and alpha-fetoprotein and liver stiffness measurement values from stage A to stage D (P < .05). ANOVA analysis showed that the overall liver stiffness measurement among the four BCLC stages was found to be statistically significant different in HBV-infected and HCV-infected HCC patients. CONCLUSION: Majority (99.24%) were patients aged >40 years old. Male is a high incidence population. In etiological analysis, HBV dominates HCC occurrence, HBV-, HCV-, and alcohol-associated HCC have distinct clinical and biochemical characteristics, necessitating different screening policies to optimize HCC surveillance and management.

4.
Plant Biol (Stuttg) ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31627255

RESUMO

Leaf venations have elements with relatively low elasticity than other leaf tissue components, which are supposed to contribute to leaf biomechanics. A better mechanistic understanding of relationships between vein traits and leaf mechanical properties is essential for ecologically relevant interpretation of leaf structural variations. We investigated 13 major (first to third order) and minor (>third order) vein traits, six leaf mechanical properties and other structural traits across 58 woody species from a subtropical forest to elucidate how vein traits contribute to leaf biomechanics. Across species, vein dry mass density (ρv), total vein dry mass per leaf area (VMA) and minor vein diameter (VDmin), but not the lower-order vein density (VLA1•2), were positively correlated with leaf force to punch (Fp) and force to tear (Ft). Structural equation model showed that ρv and VDmin would not only contribute to leaf mechanical properties directly (direct pathway), but also had impacts on leaf biomechanics by influencing leaf thickness and leaf dry mass per area (indirect pathway). Our study demonstrated that vein dry mass density and minor vein diameter are the key vein properties for leaf biomechanics. We also suggested that the mechanical characteristics of venations are the potential factors influencing leaf mechanical resistance, structures and leaf economics spectrum.

5.
Urol J ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31630384

RESUMO

PURPOSE: To investigate the clinical implications of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of patients prior to radical prostatectomy. MATERIALS AND METHODS: A total of 91 prostate cancer (PCa) patients and 50 benign prostatic hyperplasia (BPH) patients were enrolled from January 2016 to December 2017. The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of PCa and BPH patients were detected by flow cytometry, and the association of these T-cell populations with pathological Grade Group and pathological TNM classification was evaluated. Data analysis was performed with SAS version 9.4 software. RESULTS: The proportions of CD3+CD69+ and CD8+CD28+ T-cells in peripheral blood were higher in PCa patients than those in BPH patients. Multivariate analysis identified a higher CD3+CD69+ T-cell proportion as a risk factor for PCa (odds ratio (OR)=4.783, P=0.0013), but the diagnostic efficacy of the CD3+CD69+ T-cell proportion (area under the curve (AUC)=0.6833, P=0.0003) for PCa was still inferior to that of the tPSA level (AUC=0.7531, P<0.0001). The AUCs for CD3+CD69+ T-cell and CD8+CD28+ T-cell proportions for PCa were 0.6959 (P=0.0372) and 0.6935 (P=0.0395), respectively, among men with tPSA levels of 4.0-10.0 ng/ml. A lower CD3+CD69+ T-cell proportion was associated with higher pathological Grade Group (P=0.0074). CONCLUSION: The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in peripheral blood are potential diagnostic indicators for PCa. The preoperative proportion of CD3+CD69+ T-cells in peripheral blood may have prognostic value in terms of the pathological Grade Group in PCa.

6.
BMC Public Health ; 19(1): 1279, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590643

RESUMO

BACKGROUND: Studies from Western countries reported a positive relationship between residential density (RD) and physical activity (PA) among adults. There was no such study from China, a rapidly-urbanizing country in the world. This study aimed to investigate the RD-PA association among urban adults in China. METHODS: A multistage sampling approach was used to randomly select participants (aged 35-74 years old) in urban areas of Nanjing in 2017. The outcome variable was PA (dichotomized into "sufficient" or "insufficient"), while the independent variable was RD (tertiled into three sub-groups). Odds ratios (OR) and 95% confidence interval (CI) were computed to examine the RD-PA association using mixed-effects logistic regression models with adjustment for age, sex, nationality, marriage, educational attainment, employment status, body weight status, green space and neighborhood-level clustering effects. RESULTS: Of the 1568 eligible participants, 1551 were interviewed (response rate = 98.9%), with the mean age (standard deviation) of 54.7 (11.1) years old, and 46% of men. After adjustment for potential confounders and community-level clustering effects, participants lived in communities with higher (OR = 0.31, 95% CI = 0.21, 0.47) and middle (OR = 0.70, 95% CI = 0.50, 0.99) residential density were significantly less likely to achieve sufficient physical activity relative to their counterparts lived in the lower densed communities. Similar negative RD-PA association was examined for men or women, separately. The difference in the ORs between the middle and higher RD tertiles was also statistically significant (P < 0.01). CONCLUSIONS: A negatively gradient RD-PA association, independent of body weight status and green space, was observed among urban adults in regional China. It has public health implications for China to help residents' promote and maintain physical activity through planning and constructing PA-/health-friendly built environment in future.

7.
J Am Chem Soc ; 141(42): 16954-16960, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31577138

RESUMO

Aluminum(III) is inherently electron deficient and therefore acts as a prototypical Lewis acid. Conversely, Al(I) is a rare, nucleophilic variant of aluminum that is thermodynamically unstable under ambient conditions. While attempts to stabilize and isolate Al(I) species have become increasingly successful, the parent Al(I) (i.e, Al-H) remains accessible only under extreme temperatures/pressures or matrix conditions. Here, we report the isolation of the parent Al(I) hydride under ambient conditions via the reduction of a Lewis-base-stabilized alkyldihaloalane. Computational and spectroscopic analyses indicate that the ground-state electronic configuration of this monomeric aluminum species is best described as an Al(I) hydride with non-negligible open-shell Al(III) singlet diradical character. These findings are also supported by reactivity studies, which reveal both the p-centered lone pair donating ability and the hydridic nature of the parent aluminene.

8.
Phytomedicine ; 65: 153083, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31600690

RESUMO

BACKGROUND: Angiogenesis plays a critical role in ischemia disease like coronary heart disease. Shunxinyin formula has been developed for treating coronary heart disease according to the principle of traditional Chinese medicine while its underlying mechanism is not fully elucidated. PURPOSE: Here, we hypothesize Shuxinyin formula could promote angiogenesis and microcirculation, and the underlying mechanism is also investigated. METHODS: We established the chemical profile of Shuxinyin (SXY) extract utilizing a UHPLC-Q/Exactive analysis system and evaluated its pro-angiogenesis effect in zebrafish model. The underlying mechanisms were investigated by combination of pharmacological experiments with transcriptome analysis in zebrafish. Zebrafish treated with VEGF was served as the positive control in present study. RESULTS: We found SXY significantly enhanced the sub-intestinal vessel plexus (SIVs) growth in zebrafish. Co-treatment and post-treatment SXY attenuated VEGF receptor tyrosine kinase inhibitor II (VRI)-induced deficiency of intersegmental vessels (ISVs) in a concentration dependent manner. Post-treatment VEGF, which is a well-known angiogenesis driver, also partially ameliorated VRI-induced ISVs deficiency. In addition, SXY inhibited the down-regulation of VEGF receptors, including kdr, flt1 and kdrl, induced by VRI in zebrafish. The pro-angiogenesis effect of SXY on VRI-induced ISVs deficiency was suppressed by PI3K and JNK inhibitors, and Akt inhibitor abolished the pro-angiogenesis effect of SXY. The transcriptome profile of SXY preventing from VRI-induced vascular growth deficiency revealed that the underlying mechanisms were also co-related to cell junction, apoptosis and autophagy. CONCLUSION: We could conclude that SXY presented pro-angiogenesis effect and the action mechanisms were involved in VEGF/PI3K/Akt/MAPK signaling pathways, cell junction, apoptosis and autophagy.

9.
Appl Opt ; 58(26): 7205-7211, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503995

RESUMO

Since some previous methods sacrifice too much imaging quality to achieve the valid retroreflection reduction, a novel image plane tilted system combined with the wavefront coding is proposed in this paper, which could improve the privacy and security of the imaging equipment by eliminating the retroreflection without suffering significant degradation in imaging quality. First, the theoretical model of the tilted wavefront coding system is established based on the wave-optics theory. According to the derived point spread function and the modulation transfer function, the maximum tilt angle of the image plane is obtained. Second, the target system is designed and optimized by Zemax, and the later simulation analyzes the effects of the tilting on both the retroreflection and the imaging property. Finally, the experiments verify the simulation results. It shows that when the tilt angle equals 5°, there is no longer significant retroreflection on the observation plane with the total receiving power decreasing to nearly 4 orders of magnitude compared with the state without tilting. Moreover, within the maximum tilt angle, the final decoded images of the wavefront coding system still maintain superior clarity and uniformity for both the artificial and the natural objects. Consequently, the BRISQUE index is reduced by 15.92% and 28.19%, respectively, compared with the conventional imaging system, which indicates that the image quality is significantly improved by the proposed system. In conclusion, the technique of wavefront coding could effectively compensate for the high-order aberrations induced by the tilting and preserve a large field of view for precise imaging with no retroreflection, which shows us a broad prospect.

10.
Dalton Trans ; 48(40): 14962-14965, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31549712

RESUMO

The mononuclear cyclic (alkyl)(amino)carbene (cAAC) supported titanium(iii) chloride complex [(cAAC)2TiCl3] has been synthesized by treatment of free cAAC with TiCl3(THF)3. Further reduction of (cAAC)2TiCl3 with potassium graphite (KC8) afforded the desired (cAAC)2TiCl2 complex, which features a small S-T energy gap. Both complexes were structurally characterized and represent the first cAAC supported Ti complexes.

11.
Opt Express ; 27(17): 23682-23692, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510269

RESUMO

Influenced by severe ambient noises and nonstationary disturbance signals, multi-class event classification is an enormous challenge in several long-haul application fields of distributed vibration sensing technology (DVS), including perimeter security, railway safety monitoring, pipeline surveillance, etc. In this paper, a deep dual path network is introduced into solving this problem with high learning capacity. The spatial time-frequency spectrum datasets are built by utilizing the multidimensional information of DVS signal, especially the spatial domain information. With the novel datasets and a high-parameter-efficiency network, the proposed scheme presents good reliability and robustness. The feasibility is verified in an actual railway safety monitoring field test, as a proof-of-concept. Seven types of real-life disturbances were implemented and their f1-scores all reached up to 97% in the test. The performance of this proposed approach is fully evaluated and discussed. The presented approach can be employed to improve the performance of DVS in actual applications.

12.
Acta Pharmacol Sin ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515528

RESUMO

Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5-2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg(fli-1a: EGFP)y1. Timo AIII (0.5-4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment.

13.
Environ Sci Technol ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31553886

RESUMO

We use a real-time temperature-programmed desorption chemical-ionization mass spectrometer (FIGAERO-CIMS) to measure particle-phase composition and volatility of nucleated particles, studying pure α-pinene oxidation over a wide temperature range (-50 °C to +25 °C) in the CLOUD chamber at CERN. Highly oxygenated organic molecules are much more abundant in particles formed at higher temperatures, shifting the compounds toward higher O/C and lower intrinsic (300 K) volatility. We find that pure biogenic nucleation and growth depends only weakly on temperature. This is because the positive temperature dependence of degree of oxidation (and polarity) and the negative temperature dependence of volatility counteract each other. Unlike prior work that relied on estimated volatility, we directly measure volatility via calibrated temperature-programmed desorption. Our particle-phase measurements are consistent with gas-phase results and indicate that during new-particle formation from α-pinene oxidation, gas-phase chemistry directly determines the properties of materials in the condensed phase. We now have consistency between measured gas-phase product concentrations, product volatility, measured and modeled growth rates, and the particle composition over most temperatures found in the troposphere.

14.
Proc Natl Acad Sci U S A ; 116(37): 18423-18428, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31444302

RESUMO

During prophase I of meiosis, chromosomes become organized as loop arrays around the proteinaceous chromosome axis. As homologous chromosomes physically pair and recombine, the chromosome axis is integrated into the tripartite synaptonemal complex (SC) as this structure's lateral elements (LEs). While the components of the mammalian chromosome axis/LE-including meiosis-specific cohesin complexes, the axial element proteins SYCP3 and SYCP2, and the HORMA domain proteins HORMAD1 and HORMAD2-are known, the molecular organization of these components within the axis is poorly understood. Here, using expansion microscopy coupled with 2-color stochastic optical reconstruction microscopy (STORM) imaging (ExSTORM), we address these issues in mouse spermatocytes at a resolution of 10 to 20 nm. Our data show that SYCP3 and the SYCP2 C terminus, which are known to form filaments in vitro, form a compact core around which cohesin complexes, HORMADs, and the N terminus of SYCP2 are arrayed. Overall, our study provides a detailed structural view of the meiotic chromosome axis, a key organizational and regulatory component of meiotic chromosomes.

15.
JMIR Mhealth Uhealth ; 7(8): e13491, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31400104

RESUMO

BACKGROUND: The last decade has witnessed many achievements in China's health care industry, but the industry still faces major challenges among which the uneven distribution of medical resources and the imbalance between supply and demand are the most pressing problems. Although mobile health (mHealth) services play a significant role in mitigating problems associated with health care delivery, their adoption rates have been low. OBJECTIVE: The objective of this study was to explore the impact of resource scarcity and resource accessibility on the adoption of mHealth from the perspective of resource competition, to examine the concerning factors, and to provide a theoretical basis for promoting mHealth in China. METHODS: We used 229,516 original registration records of outpatients to conduct an empirical analysis to examine the adoption of mHealth services from the perspective of resource competition. RESULTS: The adoption rate of mobile services for outpatients was low, accounting for only 31.5% (N=71,707). The empirical results indicated that resource scarcity (beta=.435, P=.01) and accessibility (beta=-.134, P=.02) have a significant impact on the adoption of mHealth. In addition, gender (beta=.073, P=.01) and age (beta=-.009, P<.001) are significantly related to adoption of mHealth. Experience with mHealth has a moderating role in the relationship between resource scarcity (beta=-.129, P=.02), accessibility (beta=.138, P=.04), and adoption of mHealth. CONCLUSIONS: In this study we demonstrate that the external environment (resource scarcity and resource accessibility) has a significant impact on the adoption of mHealth. This study also demonstrates that experience with mHealth has a moderating role in the relationship between the elements of the external environment. Finally, we confirm that mHealth is a key factor in the delivery and allocation of medical resources and provide a theoretical basis for government agencies to develop policies on mHealth.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31375471

RESUMO

INTRODUCTION: Nasopharyngeal carcinoma, an epithelial-derived malignant tumor which because of its anatomical location and atypical early symptoms, when diagnosed invasion and metastasis often have occurred. This requires a better understanding of the development mechanism, identifying diagnostic markers, and developing new treatment strategies. OBJECTIVE: To study the relationship of LMP1 and Cripto-1 in nasopharyngeal carcinoma. METHODS: The expression of LMP1 and Cripto-1 in specimens obtained from nasopharyngeal carcinoma patients (n=42) and nasopharyngitis patients (n=22) were examined. The expression of LMP1 and Cripto-1 in LMP1-negative and LMP1-positive (CNE1-LMP1) cells were also examined. RESULTS: The expression of LMP1 and Cripto-1 was significantly higher in nasopharyngeal carcinoma than in nasopharyngitis (p<0.05). Their expression in nasopharyngeal carcinoma with metastasis was significantly higher than that without metastasis (p<0.05), which was correlated with TNM staging (p<0.05). High Cripto-1 expression and high proliferation rate were seen in CNE1-LMP1 cells. CONCLUSIONS: The expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma is positively related. Their co-expression might contribute to the proliferation and metastasis of nasopharyngeal carcinoma.

17.
Nat Commun ; 10(1): 3708, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420553

RESUMO

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and ß1-integrin receptors, resulting in Met/ß1-integrin co-internalization and co-accumulation on endosomes. This provides persistent signals to activate the FAK/p130Cas pathway, thereby promoting CRC cell migration, invasion and metastasis. Blocking endocytosis or endosomal Met/ß1-integrin/FAK signaling profoundly inhibits the oncogenic effects of both NRP1 variants. These findings reveal an important role for these NRP1 splice variants in the regulation of endocytic trafficking for cancer cell dissemination.

18.
Inorg Chem ; 58(17): 11279-11283, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31424208

RESUMO

Reactions between Rosenthal's zirconocene synthon, [Cp2Zr(py)Me3SiC≡CSiMe3] (py = pyridine), and two different types of bis(alkynyl) boranes, (Me3Si)2NB(C≡CSiMe3)2 and MesB(C≡CSiMe3)2 (Mes = 2,4,6-trimethylphenyl), both resulting in the formation of η5-coordinated bis(alkynyl)borane zirconocene complexes. X-ray diffraction analysis revealed their six-membered cyclic structures featuring a boat conformation with considerable Zr-B interactions. The Zr-B bonding strength and conformational lability of the ZrC4B ring are dependent on the π basicity of the exocyclic B substituent. These compounds represent the first examples of η5-coordinated acyclic boron-containing π ligands.

19.
J Zhejiang Univ Sci B ; 20(9): 753-765, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379145

RESUMO

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the DMD gene. The aim of this study is to identify pathogenic DMD variants in probands and reduce the risk of recurrence of the disease in affected families. Variations in 100 unrelated DMD/BMD patients were detected by multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS). Pathogenic variants in DMD were successfully identified in all cases, and 11 of them were novel. The most common mutations were intragenic deletions (69%), with two hotspots located in the 5' end (exons 2-19) and the central of the DMD gene (exons 45-55), while point mutations were observed in 22% patients. Further, c.1149+1G>A and c.1150-2A>G were confirmed by hybrid minigene splicing assay (HMSA). This two splice site mutations would lead to two aberrant DMD isoforms which give rise to severely truncated protein. Therefore, the clinical use of MLPA, NGS, and HMSA is an effective strategy to identify variants. Importantly, eight embryos were terminated pregnancies according to prenatal diagnosis and a healthy boy was successfully delivered by preimplantation genetic diagnosis (PGD). Early and accurate genetic diagnosis is essential for prenatal diagnosis/PGD to reduce the risk of recurrence of DMD in affected families.

20.
Pharm Biol ; 57(1): 519-528, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401926

RESUMO

Context: The interruption of cerebral blood circulation may cause stroke characterized by high neurological deficits (NDs) as a result of neuronal dysfunction or destruction. Heparin may exert a neuroprotective effect against cerebral ischaemia/reperfusion injury. Objective: The objective of this study was to investigate the mechanism underlying the effects of heparin pre-treatment on cerebral injury in the gerbil. Materials and methods: A total of 80 healthy Mongolian gerbils were randomly divided into four groups to establish cerebral ischaemia model by bilateral carotid artery occlusion: control (no anaesthesia and surgery), sham (no occlusion), non-anticoagulation (occlusion), and anti-coagulation treatment groups (50 IU/100 g heparin pre-treated, occlusion). Gerbils were anesthetized with 40 mg/kg pentobarbital sodium through intraperitoneal injection before operation except for the control group. Then, the ND and histopathological damage (HD) scores were determined. The percentage of tumour necrosis factor (TNF)-α- and interleukin (IL)-1ß-positive cells were calculated based on immunohistochemical results. The mRNA and protein levels of caspase-9, caspase-8, FasL, and calpain were evaluated with real-time polymerase chain reaction (RT-PCR) and western blotting, respectively. Results: Compared with non-anticoagulation group, heparin pre-treatment (50 IU/100 g) delayed the onset of dyspnoea (p < 0.05), and showed a significant decrease in ND (p < 0.01), mortality rate (p < 0.05), HD (p < 0.01) and percentage of positive cells for TNF-α, IL-1ß (p < 0.01) in cerebral ischaemia gerbils. Besides, the expression levels of caspase-9, caspase-8, FasL, and calpain were reduced after pre-treatment with 50 IU/100 g heparin. Discussion and conclusions: The damage caused to gerbil brain was reduced upon pre-treatment with heparin, possibly through the amelioration of neuronal cell apoptosis and expression of TNF-α and IL-1ß. These findings are expected to provide a new breakthrough in the study and treatment of cerebral ischaemia.

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